The Interactions between Hallucinogens and Antidepressants
Summary of Results from Online Survey and Online Interviews
Oct 1994From personal communication and posted to Usenet, Oct 3, 1994.
First published by Erowid in 1995.
by Kit Bonson

As many of you are aware, over the past months I have been conducting a retrospective study here at the National Institute of Mental Health on the interactions of hallucinogens and antidepressants in humans. I'm finally at a place where I can reveal my results. These data have already been presented at the Serotonin Club meeting in Chicago this summer and are in the process of being written up for submission to pharmacology/psychiatry journals (I'll post the references later, assuming the manuscripts are accepted).

Thanks to all of you on the Net who responded to my requests for subjects!

The basic idea of the study arose because I have a lot of friends who have been on antidepressants and also have a long-standing interest in hallucinogens. They would call me up (as their personal pharmacologist) and want to know why they had unusual responses to LSD while they were taking antidepressants. It turned out that the experience one had on LSD could be highly variable, dependent on which antidepressant one was taking. Based on these initial reports, I asked to interview people with similar histories by placing announcements in the local D.C. alternative newspaper, on newsgroups on the Net, and by an article in the MAPS (Multidisciplinary Association for Psychedelic Studies) newsletter. People also contacted me after hearing of the study by word of mouth or by being referred by a health professional.

Although many many people responded to my request, I was only able to use those reports where there was a "control" condition, ie: either the person had taken the same hallucinogen prior to antidepressant treatment or else had friends who had taken the same hallucinogen but were on on antidepressants. Everyone who participated was given a structured questionnaire that first asked about the person's antidepressant treatment, other drugs they regularly consumed, and past experience with hallucinogens. Then I asked about the experience the person had with a hallucinogen while taking an antidepressant. The main thing I was interested in was whether there was an increase, a decrease or no change in the person's response to the hallucinogen in terms of the time it took to get high, the physical effects, the hallucinatory effects, the psychological effects, the total time they were high, any aftereffects or alterations in sleep and then their overall impression of the trip.

In a nutshell, people who were taking serotonin-selective antidepressants or MAO inhibitors had a decrease or abolishment of their response to hallucinogens. This is in contrast to what happens when people were taking tricyclic antidepressants or lithium: they had a vast increase in their response to hallucinogens. Please note that everyone who responded had been taking antidepressants for at least 3-4 weeks, if not longer. This is the time necessary for therapeutic effects to begin, and this is thought to correlate with changes in neurotransmitter systems in the brain. We have no information about what happens when people have only taken antidepressants for a short time and then consume a hallucinogen.

Below is a more comprehensive summary of the data:

SEROTONIN-SELECTIVE ANTIDEPRESSANTS:

*Fluoxetine* (Prozac) -- even at doses of this antidepressant ranging from
2 mg/day to 40 mg/day, there was an overall decrease in most effects from LSD (no matter how much acid people took), as well as a decrease in response to ketamine. There was no change in response to psilocybin. There does seem to be a decrease in the response to MDMA.

*Sertraline* (Zoloft) -- the effect with this antidepressant seems to be dose-dependent. At 50 mg/day, there was no effect on the response to LSD nor to psilocybin. However, at 100 mg/day, there was a decrease in response to both LSD and MDMA.

*Paroxetine* (Paxil) -- decrease in response to LSD.

*Trazodone* (Desyrel) -- decrease in response to LSD.

TRICYCLIC ANTIDEPRESSANTS:

*Imipramine* (Tofranil) -- increase in response to LSD.

*Desipramine* (Norpramine) -- increase in response to LSD.

*Clomipramine* (Anafranil) -- increase in response to LSD.

LITHIUM:

(*alone* or *in combination with a tricyclic antidepressant*) --
increase in response to LSD or psilocybin.

MONOAMINE OXIDASE INHIBITOR:

*Phenelzine* (Nardil) -- decrease in response to LSD
**TAKE NOTE OF THE RESPONSE TO MDMA: combining an MAO inhibitor plus MDMA has led to a hypertensive crisis and a near-fatal response in many people!!! This could be anticipated because MDMA is a substituted amphetamine, and stimulants should not be combined with an MAO
inhibitor!!! DO NOT TRY THIS AT HOME!!!

There were a few other psychotherapeutic drugs that people combined with a hallucinogen, but you'll have to wait for the journal articles for these odd responses.

How do we explain these data?? Well, this is a bit of a theoretical problem. One would want to say that the hallucinogenic response occurs because of 5-HT-2 stimulation and therefore there was down-regulation of 5-HT-2 sites following serotonin-selective antidepressants and MAO inhibitors, thus leading to elimination of the hallucinogenic response. The problem is that these antidepressants do not always alter the brain in this way. The other, bigger, problem is that tricyclic antidepressants are thought to act very similarly to SSRI's in their ability to down-regulate 5-HT-2 sites, and thus there is no accounting for the appearance that TCA's increase response to LSD. We are at the stage now where we are trying to formulate a theory based on the difference between classes of drugs in terms of their effects on 5-HT-1A sites and in terms of the way the different antidepressant change serotonin levels. Since LSD has effects not only at 5-HT-2 sites but also at 5-HT-1A sites, this may allow for why these drugs affect the hallucinogenic response differently.

So, thanks for all the support I received from everyone who helped out with this study. All of you who participated and then kept quiet about my results receive my gratitude. Special thanks to Lamont Granquist who not only was very helpful in recruiting subjects for me and for sending me references I might have otherwise missed but restrained himself for months
from spreading the word about these interesting results.

If anyone out there knows of someone who could be a subject, they can contact me with the information below. I'm basically in the last phase of writing the manuscripts, but could still interview someone if they wanted to step forward, especially those who have used MDMA. Contact me at:
Kit Bonson, Ph.D.
kbonson@earthlink.net